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Publications (543)3061.13 Total impact
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ABSTRACT: Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selection and compare this to the observed temporal patterns of antibody evolution in HIV infection. We describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability. © 2015 The Author(s) Published by the Royal Society. All rights reserved.Philosophical Transactions of The Royal Society B Biological Sciences 09/2015; 370(1676). DOI:10.1098/rstb.2014.0247 · 7.06 Impact Factor
Article: Competitive exclusion by autologous antibodies can prevent broad HIV-1 antibodies from arising[Show abstract] [Hide abstract]
ABSTRACT: The past decade has seen the discovery of numerous broad and potent monoclonal antibodies against HIV type 1 (HIV-1). Eliciting these antibodies via vaccination appears to be remarkably difficult, not least because they arise late in infection and are highly mutated relative to germline antibody sequences. Here, using a computational model, we show that broad antibodies could in fact emerge earlier and be less mutated, but that they may be prevented from doing so as a result of competitive exclusion by the autologous antibody response. We further find that this competitive exclusion is weaker in infections founded by multiple distinct strains, with broadly neutralizing antibodies emerging earlier than in infections founded by a single strain. Our computational model simulates coevolving multitype virus and antibody populations. Broadly neutralizing antibodies may therefore be easier for the adaptive immune system to generate than previously thought. If less mutated broad antibodies exist, it may be possible to elicit them with a vaccine containing a mixture of diverse virus strains.Proceedings of the National Academy of Sciences 08/2015; DOI:10.1073/pnas.1505207112 · 9.67 Impact Factor
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ABSTRACT: Mathematically modelling changes in HCV RNA levels measured in patients who receive antiviral therapy has yielded many insights into the pathogenesis and effects of treatment on the virus. By determining how rapidly HCV is cleared when viral replication is interrupted by a therapy, one can deduce how rapidly the virus is produced in patients before treatment. This knowledge, coupled with estimates of the HCV mutation rate, enables one to estimate the frequency with which drug resistant variants arise. Modelling HCV also permits the deduction of the effectiveness of an antiviral agent at blocking HCV replication from the magnitude of the initial viral decline. One can also estimate the lifespan of an HCV-infected cell from the slope of the subsequent viral decline and determine the duration of therapy needed to cure infection. The original understanding of HCV RNA decline under interferon-based therapies obtained by modelling needed to be revised in order to interpret the HCV RNA decline kinetics seen when using direct-acting antiviral agents (DAAs). There also exist unresolved issues involving understanding therapies with combinations of DAAs, such as the presence of detectable HCV RNA at the end of therapy in patients who nonetheless have a sustained virologic response.Nature Reviews Gastroenterology & Hepatology 06/2015; 12(8). DOI:10.1038/nrgastro.2015.97 · 12.61 Impact Factor
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ABSTRACT: Background: Emerging data relating to human immunodeficiency virus type 1 (HIV-1) cure suggest that vaccination to stimulate the host immune response, particularly cytotoxic cells, may be critical to clearing of reactivated HIV-1-infected cells. However, evidence for this approach in humans is lacking, and parameters required for a vaccine are unknown because opportunities to study HIV-1 reactivation are rare. Methods: We present observations from a HIV-1 elite controller, not treated with combination antiretroviral therapy, who experienced viral reactivation following treatment for myeloma with melphalan and autologous stem cell transplantation. Mathematical modeling was performed using a standard viral dynamic model. Enzyme-linked immunospot, intracellular cytokine staining, and tetramer staining were performed on peripheral blood mononuclear cells; in vitro CD8 T-cell-mediated control of virion production by autologous CD4 T cells was quantified; and neutralizing antibody titers were measured. Results: Viral rebound was measured at 28,000 copies/mL on day 13 post-transplant before rapid decay to <50 copies/mL in 2 distinct phases with t1/2 of 0.71 days and 4.1 days. These kinetics were consistent with an expansion of cytotoxic effector cells and killing of productively infected CD4 T cells. Following transplantation, innate immune cells, including natural killer cells, recovered with virus rebound. However, most striking was the expansion of highly functional HIV-1-specific cytotoxic CD8 T cells, at numbers consistent with those applied in modeling, as virus control was regained. Conclusions: These observations provide evidence that the human immune response is capable of controlling coordinated global HIV-1 reactivation, remarkably with potency equivalent to combination antiretroviral therapy. These data will inform design of vaccines for use in HIV-1 curative interventions.Clinical Infectious Diseases 06/2015; 61(1). DOI:10.1093/cid/civ219 · 8.89 Impact Factor
Article: Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: HCV kinetic analysis and modeling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. METHODS: Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to εmax) was fit to viral kinetic data. RESULTS: Baseline viral load and age were significantly associated with the severity of liver disease (p<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline patients with less severe liver disease. The maximal effectiveness, εmax, was significantly (p≤0.032) associated with increasing severity of liver disease (εmax[s.e.]=0.86[0.05], εmax=0.69[0.06] and εmax=0.59[0.1]). . The 2(nd) phase decline slope was not significantly different among groups (mean 1.88±0.15 log10IU/ml/wk, p=0.75) as was the rate of change of SIL effectiveness (k=2.12/day[standard error, s.e.=0.18/day]). HCV-infected cell loss rate (δ[s.e.]=0.62/day[0.05/day]) was high and similar among groups. CONCLUSIONS: The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.Antiviral therapy 05/2015; 20(2):149-155. DOI:10.3851/IMP2806 · 3.02 Impact Factor
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ABSTRACT: Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infected cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.Proceedings of the National Academy of Sciences 04/2015; 112(17). DOI:10.1073/pnas.1419162112 · 9.67 Impact Factor
Article: Quantification of Hepatitis C Virus Cell-to-Cell Spread Using a Stochastic Modeling Approach[Show abstract] [Hide abstract]
ABSTRACT: It has been proposed that viral cell-to-cell transmission plays a role in establishing and maintaining chronic infections. Thus, understanding the mechanisms and kinetics of cell-to-cell spread are fundamental to elucidating the dynamics of infection and may provide insight into factors that determine chronicity. Because hepatitis C virus (HCV) spreads cell-to-cell and HCV has a chronicity rate of up to 80% in exposed individuals, we examined the dynamics of HCV cell-to-cell spread in vitro and quantified the effect of inhibiting individual host factors. Using a multidisciplinary approach, we performed HCV spread assays and assessed the appropriateness of different stochastic models for describing HCV foci expansion. To evaluate the effect of blocking specific host cell factors on HCV cell-to-cell transmission, assays were performed in the presence of blocking antibodies and/or small molecule inhibitors targeting different cellular HCV entry factors. In all experiments, HCV positive cells were identified by immunohistochemical staining and the number of HCV-positive cells per focus was counted to determine focus size. We found that HCV foci expansion can best be explained by mathematical models assuming foci size-dependent growth. Consistent with previous reports suggesting some factors impact HCV cell-to-cell spread to different extents, modeling results estimate a hierarchy of efficacies for blocking HCV cell-to-cell spread when targeting different host factors (e.g. CLDN1 > NPC1L1 > TfR1). This approach can be adapted to describe foci expansion dynamics under a variety of experimental conditions as a means to quantify cell-to-cell transmission and assess the impact of cellular factors, viral factors and antivirals. The ability of viruses to efficiently spread by direct cell-to-cell transmission is thought to play an important role the establishment and maintenance of viral persistence. As such, elucidating the dynamics of cell-to-cell spread and quantifying the effect of blocking the factors involved has important implications for the design of potent antiviral strategies and controlling viral escape. Mathematical modeling has been widely used to understand HCV infection dynamics and treatment response, however these models typically assume only cell-free virus infection mechanisms. Here, we used stochastic models describing foci expansion as a means to understand and quantify the dynamics of HCV cell-to-cell spread in vitro and determined the degree to which cell-to-cell spread is reduced when individual HCV entry factors are blocked. The results presented demonstrate the ability of this approach to recapitulate and quantify cell-to-cell transmission, as well as the impact of specific factors and potential antivirals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.Journal of Virology 04/2015; 89(13). DOI:10.1128/JVI.00016-15 · 4.44 Impact Factor
Article: Transmitted Virus Fitness and Host T Cell Responses Collectively Define Divergent Infection Outcomes in Two HIV-1 Recipients[Show abstract] [Hide abstract]
ABSTRACT: Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of T cell responses to conserved viral epitopes.PLoS Pathogens 01/2015; 11(1):e1004565. DOI:10.1371/journal.ppat.1004565 · 7.56 Impact Factor
Article: Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation[Show abstract] [Hide abstract]
ABSTRACT: Background Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses.ResultsThe T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations.Conclusions Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.Retrovirology 11/2014; 11(1):101. DOI:10.1186/s12977-014-0101-0 · 4.19 Impact Factor
Article: Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes[Show abstract] [Hide abstract]
ABSTRACT: Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV infection dynamics are still poorly understood, including the preferred mode of viral propagation, as well as the proportion of infected hepatocytes. Answers to these questions have important implications for the development of therapeutic interventions. In this study, we present methods to analyze the spatial distribution of infected hepatocytes obtained by single cell laser capture microdissection from liver biopsy samples of patients chronically infected with HCV. By characterizing the internal structure of clusters of infected cells, we are able to evaluate hypotheses about intrahepatic infection dynamics. We found that individual clusters on biopsy samples range in size from [Formula: see text] infected cells. In addition, the HCV RNA content in a cluster declines from the cell that presumably founded the cluster to cells at the maximal cluster extension. These observations support the idea that HCV infection in the liver is seeded randomly (e.g. from the blood) and then spreads locally. Assuming that the amount of intracellular HCV RNA is a proxy for how long a cell has been infected, we estimate based on models of intracellular HCV RNA replication and accumulation that cells in clusters have been infected on average for less than a week. Further, we do not find a relationship between the cluster size and the estimated cluster expansion time. Our method represents a novel approach to make inferences about infection dynamics in solid tissues from static spatial data.PLoS Computational Biology 11/2014; 10(11):e1003934. DOI:10.1371/journal.pcbi.1003934 · 4.62 Impact Factor
Article: A pharmacokinetic/viral kinetic model to evaluate the treatment effectiveness of danoprevir against chronic HCV[Show abstract] [Hide abstract]
ABSTRACT: Background: Viral kinetic models have proven useful to characterize treatment effectiveness during HCV therapy with interferon (IFN) or with direct-acting antivirals. Methods: We use a pharmacokinetic/viral kinetic (PK/VK) model to describe HCV RNA kinetics during treatment with danoprevir, a protease inhibitor. In a Phase I study, danoprevir monotherapy was administered for 14 days in ascending doses ranging from 200 to 600 mg per day to 40 patients of whom 32 were treatment-naive and 8 were non-responders to prior pegylated IFN-α/ribavirin treatment. Results: In all patients, a biphasic decline of HCV RNA during therapy was observed. A two-compartment PK model and a VK model that considered treatment effectiveness to vary with the predicted danoprevir concentration inside the second compartment provided a good fit to the viral load data. A time-varying effectiveness model was also used to fit the viral load data. The antiviral effectiveness increased in a dose-dependent manner, with a 14-day time-averaged effectiveness of 0.95 at the lowest dose (100 mg twice daily) and 0.99 at the highest dose (200 mg three times daily). Prior IFN non-responders exhibited a 14-day time-averaged effectiveness of 0.98 (300 mg twice daily). The second phase decline showed two different behaviours, with 30% of patients exhibiting a rapid decline of HCV RNA, comparable to that seen with other protease inhibitors (>0.3 day(-1)), whereas the viral decline was slower in the other patients. Conclusions: Our results are consistent with the modest SVR rates from the INFORM-SVR study where patients were treated with a combination of mericitabine and ritonavir-boosted danoprevir.Antiviral therapy 10/2014; DOI:10.3851/IMP2879 · 3.02 Impact Factor
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ABSTRACT: HIV-1-infected cells in peripheral blood can be grouped into different transcriptional subclasses. Quantifying the turnover of these cellular subclasses can provide important insights into the viral life cycle and the generation and maintenance of latently infected cells. We used previously published data from five patients chronically infected with HIV-1 that initiated combination antiretroviral therapy (cART). Patient-matched PCR for unspliced and multiply spliced viral RNAs combined with limiting dilution analysis provided measurements of transcriptional profiles at the single cell level. Furthermore, measurement of intracellular transcripts and extracellular virion-enclosed HIV-1 RNA allowed us to distinguish productive from non-productive cells. We developed a mathematical model describing the dynamics of plasma virus and the transcriptional subclasses of HIV-1-infected cells. Fitting the model to the data allowed us to better understand the phenotype of different transcriptional subclasses and their contribution to the overall turnover of HIV-1 before and during cART. The average number of virus-producing cells in peripheral blood is small during chronic infection. We find that a substantial fraction of cells can become defectively infected. Assuming that the infection is homogenous throughout the body, we estimate an average in vivo viral burst size on the order of 104 virions per cell. Our study provides novel quantitative insights into the turnover and development of different subclasses of HIV-1-infected cells, and indicates that cells containing solely unspliced viral RNA are a good marker for viral latency. The model illustrates how the pool of latently infected cells becomes rapidly established during the first months of acute infection and continues to increase slowly during the first years of chronic infection. Having a detailed understanding of this process will be useful for the evaluation of viral eradication strategies that aim to deplete the latent reservoir of HIV-1.PLoS Computational Biology 10/2014; 10(10):e1003871. DOI:10.1371/journal.pcbi.1003871 · 4.62 Impact Factor
Article: Modeling the Dynamics and Migratory Pathways of Virus-Specific Antibody-Secreting Cell Populations in Primary Influenza Infection[Show abstract] [Hide abstract]
ABSTRACT: The B cell response to influenza infection of the respiratory tract contributes to viral clearance and establishes profound resistance to reinfection by related viruses. Numerous studies have measured virus-specific antibody-secreting cell (ASC) frequencies in different anatomical compartments after influenza infection and provided a general picture of the kinetics of ASC formation and dispersion. However, the dynamics of ASC populations are difficult to determine experimentally and have received little attention. Here, we applied mathematical modeling to investigate the dynamics of ASC growth, death, and migration over the 2-week period following primary influenza infection in mice. Experimental data for model fitting came from high frequency measurements of virus-specific IgM, IgG, and IgA ASCs in the mediastinal lymph node (MLN), spleen, and lung. Model construction was based on a set of assumptions about ASC gain and loss from the sampled sites, and also on the directionality of ASC trafficking pathways. Most notably, modeling results suggest that differences in ASC fate and trafficking patterns reflect the site of formation and the expressed antibody class. Essentially all early IgA ASCs in the MLN migrated to spleen or lung, whereas cell death was likely the major reason for IgM and IgG ASC loss from the MLN. In contrast, the spleen contributed most of the IgM and IgG ASCs that migrated to the lung, but essentially none of the IgA ASCs. This finding points to a critical role for regional lymph nodes such as the MLN in the rapid generation of IgA ASCs that seed the lung. Results for the MLN also suggest that ASC death is a significant early feature of the B cell response. Overall, our analysis is consistent with accepted concepts in many regards, but it also indicates novel features of the B cell response to influenza that warrant further investigation.PLoS ONE 08/2014; 9(8):e104781. DOI:10.1371/journal.pone.0104781 · 3.23 Impact Factor
Article: A Hepatitis C Virus Infection Model with Time-Varying Drug Effectiveness: Solution and Analysis[Show abstract] [Hide abstract]
ABSTRACT: Simple models of therapy for viral diseases such as hepatitis C virus (HCV) or human immunodeficiency virus assume that, once therapy is started, the drug has a constant effectiveness. More realistic models have assumed either that the drug effectiveness depends on the drug concentration or that the effectiveness varies over time. Here a previously introduced varying-effectiveness (VE) model is studied mathematically in the context of HCV infection. We show that while the model is linear, it has no closed-form solution due to the time-varying nature of the effectiveness. We then show that the model can be transformed into a Bessel equation and derive an analytic solution in terms of modified Bessel functions, which are defined as infinite series, with time-varying arguments. Fitting the solution to data from HCV infected patients under therapy has yielded values for the parameters in the model. We show that for biologically realistic parameters, the predicted viral decay on therapy is generally biphasic and resembles that predicted by constant-effectiveness (CE) models. We introduce a general method for determining the time at which the transition between decay phases occurs based on calculating the point of maximum curvature of the viral decay curve. For the parameter regimes of interest, we also find approximate solutions for the VE model and establish the asymptotic behavior of the system. We show that the rate of second phase decay is determined by the death rate of infected cells multiplied by the maximum effectiveness of therapy, whereas the rate of first phase decline depends on multiple parameters including the rate of increase of drug effectiveness with time.PLoS Computational Biology 08/2014; 10(8):e1003769. DOI:10.1371/journal.pcbi.1003769 · 4.62 Impact Factor
Article: Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients[Show abstract] [Hide abstract]
ABSTRACT: The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients co-infected with HIV. Co-infection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV co-infected patients into a cART initiation trial and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in increased HCV replication and increased alanine aminotransferase (ALT) in a subset of patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in co-infected patients who underwent successful cART. The effective suppression of HIV by cART initiated a cascade of early and late events in treated patients. Early events involving down-regulation of interferon-stimulated genes may have led to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declined to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV co-infection.Science translational medicine 07/2014; 6(246):246ra98. DOI:10.1126/scitranslmed.3008195 · 15.84 Impact Factor
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ABSTRACT: scitranslmed.3008195 , 246ra98 (2014); 6 Sci Transl Med et al. Kenneth E. Sherman HCV/HIV co-infected patients Modulation of HCV replication after combination antiretroviral therapy in Editor's Summary infection. HIV suppression with antiretroviral medications plays an important role in the management of those with HCV and HIV This process is highly modulated by responses of the interferon-responsive gene family. The findings suggest that viral replication and evidence of liver injury. Over time, however, HIV suppression leads to reduced HCV replication. biological effects. They show that the initial response to effective HIV treatment results in a transient increase in HCV try and unravel some of these et al. virus (HCV). In a new study of patients co-infected with HCV and HIV, Sherman There is a complex interaction of biological effects when patients are infected with both HIV and the hepatitis CScience translational medicine 07/2014; 6(246):98. · 15.84 Impact Factor
Article: Reversion and T Cell Escape Mutations Compensate the Fitness Loss of a CD8 T Cell Escape Mutant in Their Cognate Transmitted/Founder Virus[Show abstract] [Hide abstract]
ABSTRACT: Immune escape mutations that revert back to the consensus sequence frequently occur in newly HIV-1-infected individuals and have been thought to render the viruses more fit. However, their impact on viral fitness and their interaction with other immune escape mutations have not been evaluated in the background of their cognate transmitted/founder (T/F) viral genomes. To precisely determine the role of reversion mutations, we introduced reversion mutations alone or together with CD8+ T cell escape mutations in their unmodified cognate T/F viral genome and determined their impact on viral fitness in primary CD4+ T cells. Two reversion mutations, V247I and I64T, were identified in Gag and Tat, respectively, but neither had measurable effect on the fitness of their cognate T/F virus. The V247I and G248A mutations that were detected before and concurrently with the potent T cell escape mutation T242N, respectively, were selected by early T cell responses. The V247I or the G248A mutation alone partially restored the fitness loss caused by the T242N mutation. Together they could fully restore the fitness of the T242N mutant to the T/F level. These results demonstrate that the fitness loss caused by a T cell escape mutation could be compensated by preexisting or concurrent reversion and other T cell escape mutations. Our findings indicate that the overall viral fitness is modulated by the complex interplay among T cell escape, compensatory and reversion mutations to maintain the balance between immune escape and viral replication capacity.PLoS ONE 07/2014; 9(7):e102734. DOI:10.1371/journal.pone.0102734 · 3.23 Impact Factor
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ABSTRACT: Hepatitis B is a DNA virus that infects liver cells and can cause both acute and chronic disease. It is believed that both viral and host factors are responsible for determining whether the infection is cleared or becomes chronic. Here we investigate the mechanism of protection by developing a mathematical model of the antibody response following hepatitis B virus (HBV) infection. We fitted the model to data from seven infected adults identified during acute infection and determined the ability of the virus to escape neutralization through overproduction of non-infectious subviral particles, which have HBs proteins on their surface, but do not contain nucleocapsid protein and viral nucleic acids. We showed that viral clearance can be achieved for high anti-HBV antibody levels, as in vaccinated individuals, when: (1) the rate of synthesis of hepatitis B subviral particles is slow; (2) the rate of synthesis of hepatitis B subviral particles is high but either anti-HBV antibody production is fast, the antibody affinity is high, or the levels of pre-existent HBV-specific antibody at the time of infection are high, as could be attained by vaccination. We further showed that viral clearance can be achieved for low equilibrium anti-HBV antibody levels, as in unvaccinated individuals, when a strong cellular immune response controls early infection.PLoS Computational Biology 07/2014; 10(7):e1003730. DOI:10.1371/journal.pcbi.1003730 · 4.62 Impact Factor
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ABSTRACT: Viral kinetic (VK) modeling has led to increased understanding of the within host dynamics of viral infections and the effects of therapy. Here we review recent developments in the modeling of viral infection kinetics with emphasis on two infectious diseases: hepatitis C and influenza. We review how VK modeling has evolved from simple models of viral infections treated with a drug or drug cocktail with an assumed constant effectiveness to models that incorporate drug pharmacokinetics and pharmacodynamics, as well as phenomenological models that simply assume drugs have time varying-effectiveness. We also discuss multiscale models that include intracellular events in viral replication, models of drug-resistance, models that include innate and adaptive immune responses and models that incorporate cell-to-cell spread of infection. Overall, VK modeling has provided new insights into the understanding of the disease progression and the modes of action of several drugs. We expect that VK modeling will be increasingly used in the coming years to optimize drug regimens in order to improve therapeutic outcomes and treatment tolerability for infectious diseases.Journal of Pharmacokinetics and Pharmacodynamics 06/2014; 41(5):431-443. DOI:10.1007/s10928-014-9363-3 · 1.86 Impact Factor
Article: Modeling viral kinetics and treatment outcome during alisporivir interferon-free treatment in hepatitis C virus genotype 2 and 3 patients: HEPATOLOGY, Vol. XX, NO. X, 2014 GUEDJ ET AL.[Show abstract] [Hide abstract]
ABSTRACT: Unlabelled: Alisporivir (ALV) is a cyclophilin inhibitor with pan-genotypic activity against hepatitis C virus (HCV). Here, we characterize the viral kinetics observed in 249 patients infected with HCV genotypes 2 or 3 and treated for 6 weeks with different doses of ALV with or without ribavirin (RBV). We use this model to predict the effects of treatment duration and different doses of ALV plus RBV on sustained virologic response (SVR). Continuous viral decline was observed in 214 (86%) patients that could be well described by the model. All doses led to a high level of antiviral effectiveness equal to 0.98, 0.96, and 0.90 in patients treated with 1,000, 800, and 600 mg of ALV once-daily, respectively. Patients that received RBV had a significantly faster rate of viral decline, which was attributed to an enhanced loss rate of infected cells, δ (mean δ = 0.35 d(-1) vs. 0.21 d(-1) in patients ± RBV, respectively; P = 0.0001). The remaining 35 patients (14%) had a suboptimal response with flat or increasing levels of HCV RNA after 1 week of treatment, which was associated with ALV monotherapy, high body weight, and low RBV levels in patients that received ALV plus RBV. Assuming full compliance and the same proportion of suboptimal responders, the model predicted 71% and 79% SVR after ALV 400 mg with RBV 400 mg twice-daily for 24 and 36 weeks, respectively. The model predicted that response-guided treatment could allow a reduction in mean treatment duration to 25.3 weeks and attain a 78.6% SVR rate. Conclusion: ALV plus RBV may represent an effective IFN-free treatment that is predicted to achieve high SVR rates in patients with HCV genotype 2 or 3 infection.Hepatology 05/2014; 59(5). DOI:10.1002/hep.26989 · 11.06 Impact Factor
Top Journals
Los Alamos National Laboratory
Лос-Аламос, California, United States
- • Theoretical Biology and Biophysics Group
- • Theoretical Division
Universiteit TwenteEnschede, Overijssel, Netherlands
Santa Fe InstituteSanta Fe, New Mexico, United States
University Center Rochester
Rochester, Minnesota, United States
- Department of Medicine
University of North Carolina at Chapel Hill
North Carolina, United States
- Department of Medicine
Massachusetts General HospitalBoston, Massachusetts, United States
University of Rochester
Rochester, NY, United States
- Department of Biostatistics and Computational Biology
Friedrich-Alexander Universität Erlangen-NürnbergErlangen, Bavaria, Germany
Wisconsin National Primate Research CenterMadison, Wisconsin, United States
Purdue University
ウェストラファイエット, Indiana, United States
- Department of Mathematics
The Rockefeller University
New York, New York, United States
- • Laboratory of Virology and Infectious Disease
- • Aaron Diamond AIDS Research Center (ADARC)
University of Illinois at Chicago
Chicago, Illinois, United States
- Department of Pharmacy Practice
University Medical Center Utrecht
Utrecht, Provincie Utrecht, Netherlands
- Department of Immunology
Weill Cornell Medical College
New York City, New York, United States
- Center for the Study of Hepatitis C
University of New South Wales
Kensington, New South Wales, Australia
- Centre for Vascular Research (CVR)
Prince of Wales Hospital and Community Health ServicesSydney, New South Wales, Australia
Columbia UniversityNew York, New York, United States
University of OxfordOxford, England, United Kingdom
University of New Mexico
Albuquerque, New Mexico, United States
- Department of Computer Science
University of Michigan
Ann Arbor, MI, United States
- • Department of Mathematics
- • Division of Computer Science and Engineering
Cornell University
Ithaca, NY, United States
- Department of Ecology and Evolutionary Biology
University of California, San Diego
San Diego, CA, United States
- Division of Infectious Diseases
Royal Melbourne HospitalMelbourne, Victoria, Australia
Brigham Young University - Provo Main CampusProvo, Utah, United States
Northern Arizona University
Flagstaff, Arizona, United States
- Department of Chemistry and Biochemistry
Bar Ilan University
Ramat Gan, Tel Aviv, Israel
- Faculty of Life Sciences
Harvard University
Cambridge, Massachusetts, United States
- Department of Molecular and Cell Biology
Utrecht University
Utrecht, Utrecht, Netherlands
- Division of Theoretical Biology and Bioinformatics
Princeton University
Princeton, NJ, United States
- • Department of Molecular Biology
- • Department of Chemical and Biological Engineering
Stanford University
Stanford, CA, United States
- Department of Mathematics
University of California, Berkeley
Berkeley, California, United States
- Lawrence Berkeley Laboratory
University of Auckland
Auckland, Auckland, New Zealand
- Department of Mathematics
Brown University
Providence, Rhode Island, United States
- • The Lefschetz Center for Dynamical Systems
- • Division of Biology and Medicine
National Institutes of Health베서스다, Maryland, United States
University of California, Los AngelesLos Ángeles, California, United States


text:
140 comments found.
My client would like the front page to just be a background image and his logo in the middle. When you click on the logo, you are then taken to the 'About' page (very similar to a landing page). I've been trying to find a way to do this but without any luck. I can't find a way to turn off the side bar in the home page only and keep it in the rest of the pages.
Unfortunately there is no option for that. You would need to manually customize the theme code. Note that the related code for the side panel is in the "header.php" file.
Thanks. Will try to fiddle with it some more.
problems with the retina plugin when trying to upload xml file.
error message;
is this related to the wordpress 4.1.1 version??
Hi there!
Hmm. I have never seen this issue on my end (WP4.1.1 too). Please firstly make sure that you have the latest plugin version installed.
For the plugin support, I would suggest to directly post your query on the plugin's support forum: https://wordpress.org/support/plugin/wp-retina-2x
hi support, i have purchased the theme and everything is perfect. however, i noticed there is an issue in IE browser. if you see this http://www.trison.com.sg/switching-power-supply-2/, there are two images not showed up at all (Click product->Switching Power Supply), when you move over on 2nd row, it shows product information on tooltip but images not displayed. could you pls advise? thank you very much Felix
Hi there!
I have checked your site on IE9, IE10 and IE11 and it looks good. I could see the product images on that page. Just wondering what version of IE you used to test?
by right, there are 13 images (7 rows), but if you see the page using IE 11, it only shows 6 rows. one row actually is missing. pls help verify. thank you
Hmm, I still could see all 13 images, 7 rows, on my IE11 (screenshot: http://cl.ly/image/0i3Y0d1x2M0L ). Please try clearing all the caches and also try checking on another machine.
I am trying to create a site using this theme, but there appears to be an issue with the permalinks.
The site is www.house-on-fire.com
Whenever i try and view any page, it just says that it cannot be displayed.
Hi there!
Not sure what kind of issue you got. I also could not see your site. The given URL just displays the Coming Soon page. Could you please elaborate, perhaps with screenshot?
Hi and thank you for great theme! I've just update the theme with VC plugun and It is stopped work: when I try to add text block it will load pop-up frame, show loading icon and nothing happend. What can I do to fix it?
Hi there!
If that does not help, please open a private ticket and send me the site URL and login account. I will check that.
Hello and thank you for answer, I've sent you private message with login-password, did you received it?
Yes. I already responded to your email about 10 hours ago. Please also check your spam inbox. It may be in there.
Hello, I am thinking of buying this theme.
On the portfolio page is it possible automatically hide / remove all the extra info so it just displays the background image?
Hi there!
Thanks for your interest.
Yes, you can set to hide the content area of portfolio single page on load.
Hello, great theme..
Is it possible on mobile view to not have the space at the beginning which is reserved for the slider background image?
I would like the background image to still be visible but for the content to overlay the background image and not be underneath it.
Unfortunately there is no option for that by default. You would need to use custom CSS to adjust that. Please try using this:
@media only screen and (max-width: 1160px) { #content-container { top: 20%; z-index: 50; } }
Put it into the "Style Customizer > Others > Custom CSS". This should help.
For how to adjust the CSS for responsive viewport, please read here: https://uxbarn.ticksy.com/article/2591/
Hi there,
A couple CSS questions:
1) I was wondering how to increase the opacity behind the photos in the full screen slider?
2) Less important- Is there any way to have a fixed image frame for the fullscreen slider photos so the arrows don't move depending on the image size?
That's all. Thank you in advance.
1. Did you mean to opacity of the content area? If so, please go to "Style Customizer > Content" and there you will see the option to set the opacity.
2. Hmm. Not sure which arrows you mentioned about. Also, the fullscreen slider by default should stretch the photos to fit the entire screen for any image sizes. Could you please elaborate and send me the URL so I could have a look?
1) Sorry, I was talking about the darkness behind photo when you open the fullscreen slider photos. It's the dark space that fills in around the photo slider when a photo is up.
2) No worries on this one, I'll just need to build my slider photos to be the same size.
3) This one came up overnight – On Mobile, when viewing the main portfolio items, you first have to click the image to get the title to pop up and then click a second time to go into that portfolio piece. I was wondering if there is a way to eliminate the double click and get it to just one?
Thanks! You guys are great.
Ah – 1) The "portfolio photo slideshow" not the full screen slider. Got the two mixed up.
1. So you mean the background opacity of the lightbox just like in this screenshot? http://cl.ly/image/2j240h1f0Y3m
If yes, you would need to manually edit the JS code to adjust that. In "/js/kose.js" file, please find this code:
overlay: { locked: false, // to prevent page jumping to the top when clicking on the object }
Then add one more line of code as:
overlay: { locked: false, // to prevent page jumping to the top when clicking on the object css: { 'background': 'rgba(0, 0, 0, 1)' }, }
You can adjust the "rgba" value here for the background color and opacity. Note that the theme uses Fancybox as a lightbox engine. You can find more of its API here: http://fancyapps.com/fancybox/
3. Unfortunately not by default. I think that is the behavior of the "hover" state on any touch devices. For the workaround to change this, you can try google with keywords like "one click hover link on mobile".
Perfect. Thanks for all of your help!
You're welcome! Glad I could help!
Hi, quick pre-sale question if I may…
Is it possible for the homepage to have the same layout as the about us page?
Thanks for your interest!
Yes, you can do that. On the demo site, the content area on homepage is set to be hidden so it shows only the fullscreen slider.
And if you want the same layout as About Us page, after importing the dummy data from the XML file, you can just copy the template from About Us to the homepage.
I have a question regarding the portfolio page. Is it possible to see the title of the portfolio item in that circle always not only on hover?
For my client it is important that the portfolio image is described by the item title. On hover I only want to have that grayscale filter. Is there any chance?
Hi there!
Yes, you can use custom CSS to force it to show up:
.uxb-port-element-item-hover { opacity: 1 !important; }
This should help!
Works well!
I thought I have to look for display: none and display: block
Thanks, great theme
Hi, Great theme! Is there a way to add a background image for lightbox previews? My customer wants to add an image behind these images… http://brynharrisonweddings.com/wp-content/uploads/2015/05/IMG_3583.jpg Thanks! Terry
One more issue…sorry! I've added a couple of "right click" blockers and they aren't working like when you click on that link above. Any ideas?
Hi Terry!
1. Did you mean to use image as a background when viewing on lightbox of the gallery grid? If so, you can try to use custom CSS to set that. For example:
.fancybox-overlay-fixed { background: url(http://brynharrisonweddings.com/wp-content/uploads/2015/05/IMG_3583.jpg) no-repeat; background-size: cover; }
In case you would like to use custom CSS for other elements, I would recommend "Developer Tools" on Chrome or "Firebug" on Firefox to inspect the elements on the page. Then you can know which CSS selector to adjust.
2. Hmm, I am not sure I understand it correctly. What did you mean by "not working like when you click on that link above"? Please also try checking the browser's console for any error messages.
Anyway, if you are using the right-click blocker from any plugin, I would suggest to contact the plugin author directly for the support.
Hi, quite a beautiful theme ! Just a quick question.
I'm currently working for a client who is looking for this kind of portfolio display, for his hotel's website But a big part of the website for him is a way for his customers to easily leave notes or comments about their stay.
I only see the testimonial section which IMO might not be enough.
Do you have anything like what I'm searching for on your template ? Thanks
Hi there!
Thanks for your interest!
If it is about WP general commenting on the portfolio single page (just like normal blog post), you can enable that section in the theme. The comment section will display right below the portfolio content.
Ok thank you for the response
Oh and another question sorry about that.
When you enlarge the portfolio details (when you click "single portfolio" and the yellow cross) you have a list of characteristics such as date, website or client.
Are those characteristics customisable ? If I want to write "Dimensions" instead of client for example Thanks
There is no direct option to change that on the WP backend. But yes, it is customizable by editing the text in the theme file.
I was wondering if you could help me with some css to eliminate the caption animation delay. I would like it to have no delay on any slide.
I noticed another post directing to the [ marginTop : $(caption).outerHeight()/2 * -1, ] is it possible to not edit the plugin file and just use css?
Hi there!
Please try using this custom CSS to override that:
.slide-caption-wrapper { margin-top: -190px !important; }
It should override the caption movement by the JS code.
Great. That eliminated the movement. Now, is there any way to eliminate the delay? I would like it to be visible as soon as the picture comes up.
Long story short: I'm using the same caption on all 3 photos and would like it to not move from the screen while switching photos.
Thank you!!
Here you go:
.slide-caption-wrapper { margin-top: -190px !important; opacity: 1 !important; }
Hope this helps!
You are awesome, worked perfectly. Thank you!!
Hi there,
I dont need the submenu on tablet and smartphone. I tried to disable it with CSS but didnt work.
Is it possible to use in the mobile version another wordpress navigation where I dont add any submenus? Or is there another way to hide the submenu in responisve version?
Thanks for supporting me
Another question: the background image from the about page in the demo: is that an stockphoto or can I buy it anywhere?
Hi there!
1. Unfortunately there is no option to disable submenu on mobile. You would need to manually edit the JS code for generating the mobile menu in "/js/kose.js" file, in the function of "initMobileMenu()".
2. Yes, it is a stock photo from Photodune. You can find it here: http://photodune.net/item/lion/4029570
Hi there,
Love this theme.
I have a client who is a voice actor and would like this theme if she can simply use her headshot as the background. Is it possible to set this image as a static background that is maintained as each page content is loaded?
Thank you!
Hi there!
Thanks for your interest! You can set the fullscreen background image on each page but if you meant to upload one global image to be used on all pages, unfortunately, there is no option for that out of the box. You might need to use custom CSS to set that.
Thanks for this. Also wondering what social media icons you have built into this i.e. LinkedIn, Youtube, etc. Also, is it possible to modify the coding so that the "//" symbols are not next to the menu item that is selected?
Default social icons that are included in the theme are: Facebook, Twitter, Google+, LinkedIn, Flickr, Behance, Dribbble, Forrst, Vimeo, YouTube, and RSS. But you can also choose to create your own custom set and use it instead.
And, yes, you can use custom CSS to override the default one to remove the "//" symbols.
hi! I've some problem to display some content with visual composer There is content in visuel composer but nothing display on front office exemple -> http://www.qwadagency.com/cap.jpg
Are you using the latest version of the theme? If not, please update the theme first then try it again. See if it helps.
But if it is already the latest version, please open a private ticket at https://uxbarn.ticksy.com/ and send me your site URL with the login account. I will check that.
Hello, I have problem with this google font: Julius+Sans+One How can I do? Thank you very much Best regards
Already responded to your ticket on https://uxbarn.ticksy.com/
Very new at this! How can I implement the Full Screen slider?
Hi there!
For the detailed steps, please see in the provided documentation, under the section of "How to > Create Page with Fullscreen Slider".
Hi, just a quick question : when are you planning to release an update for WP 4.3? Thanks in advance for your feed-back.
Hi there!
The current version (v1.4.1) can be working normally with WP4.3. I forgot to update the item description.
Anyway, I also have a plan to update the bundled plugins soon.
Hello! I love the theme! Overall it is the best I've ever used. I have one question regarding spacing. On larger desktop monitors the gap between the menu panel and the content area becomes really too large. I can see that each of the two areas are justified to the edges. Is there a way to justify the content area relative to the menu panel instead? Or centre both of them with a defined space between them? My site is piramidesandinas.com. Thanks for any help you can give me.
Hi there!
Thanks! Glad to hear you like the theme!
For your question, unfortunately, by default the content area position is relative to its container only. But you can use custom CSS to adjust the right position of it by using something like this:
#content-container, #content-toggle-buttons { right: 5%; }
Just put the code into "Style Customizer > Others > Custom CSS" box.
In case you would like to use custom CSS for other elements, I would recommend Developer Tools on Chrome or Firebug on Firefox to inspect the elements on the page. Then you can know which CSS selector to adjust.
Oh, thanks! That helps a great deal.
One other thing. I'd like to use this theme for another website, but each time I'm trying to install it is says: "The package could not be installed. No valid plugins were found. Plugin install failed." Do I need to purchase another regular licence or is something wrong with what I'm doing? I've tried various downloads from here.
Actually a license is permitted for only one website (single end product). You can see the license details here: http://themeforest.net/licenses/standard . But the error in this case is not related to the license. You can try the manual installation via FTP instead (please see the step 1 in the provided doc for details).

subset: commoncrawl


text: Ashford Hospitality Trust Company Profile (NYSE:AHT) Analyst RatingsEarningsDividendsInsider TradesCompany ProfileSocial ActivityToday's Chart Consensus Ratings for Ashford Hospitality Trust (NYSE:AHT) (?) The ratings breakdown includes the most recent rating from each analyst that has rated the stock within the last twelve months. The ratings score is a calculation of the average number of sell, hold, buy and strong buy ratings (0-1.5 = Sell, 1.5-2.5 = Hold, 2.5-3.5 = Buy, >3.5 = Strong Buy). The consensus price target is a mean average of the most recent price target set by each analyst that has set a price target for the stock in the last twelve months.Ratings Breakdown: 1 Sell Rating(s), 1 Hold Rating(s), 7 Buy Rating(s)Consensus Rating:Buy (Score: 2.67)Consensus Price Target: $11.45 (62.87% upside) Current Analysts' Coverage Summary for Ashford Hospitality Trust (NYSE:AHT) Show: All Ratings For This Stock Only the Most Recent Rating From Each Brokerage DateFirmActionRatingPrice TargetActions10/8/2015Canaccord GenuityLower Price Target$12.00 -> $10.00 8/20/2015Credit SuisseLower Price TargetNeutral$10.00 -> $9.00 8/14/2015SunTrustLower Price Target$10.50 -> $9.50 8/12/2015Bank of AmericaDowngradeBuy -> Underperform$12.00 -> $10.00 8/11/2015JMP SecuritiesLower Price TargetMarket Outperform$14.00 -> $10.00 8/10/2015Deutsche BankReiterated RatingBuy$14.00 8/9/2015Cantor FitzgeraldReiterated RatingBuy$12.00 7/13/2015Brean CapitalInitiated CoverageBuy$14.00 6/8/2015Robert W. BairdLower Price TargetOutperform$13.00 -> $12.00 3/9/2015MLV & Co.Reiterated RatingBuy$14.00 9/30/2014FBR & Co.UpgradeMarket Perform -> Outperform 5/12/2014R. F. LaffertyBoost Price TargetNeutral -> Buy$12.40 -> $14.60 3/3/2014Craig HallumDowngradeBuy -> Hold$12.00 11/3/2013Morgan StanleyReiterated RatingHold$14.00 (Data available from 10/10/2013 forward) Earnings History for Ashford Hospitality Trust (NYSE:AHT)DateQuarterConsensus EstimateActual EPSRevenue EstimateActual RevenueRelease LinkConference CallActions8/6/2015Q215$0.45$0.49$323.58 million$369.30 millionViewN/A 5/7/2015Q115$0.26$0.30$218.83 million$250.20 millionViewN/A 2/26/2015Q4$0.12$0.17$193.46 million$190.36 millionViewN/A 10/30/2014Q314$0.23$0.25$212.90 millionViewN/A 8/7/2014Q214$0.42$0.39$222.96 million$208.90 millionViewN/A 5/8/2014Q114$0.22$0.25$194.80 million$195.59 millionViewN/A 2/27/2014Q413$0.23$0.14$186.00 million$163.00 millionViewN/A 10/24/2013Q313$0.36$0.25$243.89 million$242.02 millionViewN/A 7/31/2013Q2 2013$0.59$0.55$261.96 million$258.54 millionViewN/A 5/8/2013Q113$0.36$0.35$217.06 million$231.94 millionViewN/A 2/27/2013Q412$0.38$0.39$240.33 million$240.60 millionViewN/A 10/31/2012$0.32$0.31ViewN/A 8/1/2012$0.56$0.52ViewN/A 4/25/2012$0.33$0.28ViewN/A 2/22/2012$0.41$0.42ViewN/A 11/9/2011$0.39$0.39ViewN/A (Data available from 1/1/2011 forward) Dividend History for Ashford Hospitality Trust (NYSE:AHT)AnnouncedPeriodAmountYieldEx-Dividend DateRecord DatePayable DateShare9/15/2015quarterly$0.126.37%9/28/20159/30/201510/15/2015 6/15/2015quarterly$0.126.12%6/26/20156/30/20157/15/2015 3/16/2015quarterly$0.124.88%3/27/20153/31/20154/15/2015 12/16/2014quarterly$0.124.73%12/29/201412/31/20141/15/2015 9/15/2014quarterly$0.124.34%9/26/20149/30/201410/15/2014 6/13/2014quarterly$0.534.58%6/26/20146/30/20147/15/2014 3/17/2014quarterly$0.124.27%3/27/20143/31/20144/15/2014 12/16/2013quarterly$0.125.9%12/27/201312/31/20131/15/2014 9/13/2013quarterly$0.123.9%9/26/20139/30/201310/15/2013 6/14/2013quarterly$0.123.43%6/26/20136/28/20137/15/2013 3/15/2013quarterly$0.123.93%3/26/20133/29/20134/15/2013 12/17/2012quarterly$0.114.46%12/27/201212/31/20121/15/2013 (Data available from 1/1/2013 forward) Insider Trading History for Ashford Hospitality Trust (NYSE:AHT)Transaction DateInsider NameTitleBuy/SellNumber of SharesAverage Share PriceTotal TransactionActions2/5/2015Douglas A KesslerPresidentSell47,538$10.71$509,131.98 2/4/2015Douglas A KesslerPresidentSell69,974$10.69$748,022.06 2/2/2015Douglas A KesslerPresidentSell1,581$10.66$16,853.46 1/30/2015Douglas A KesslerPresidentSell20,001$10.66$213,210.66 1/28/2015Douglas A KesslerPresidentSell6,956$11.03$76,724.68 1/26/2015Douglas A KesslerPresidentSell3,044$11.03$33,575.32 12/24/2014Douglas A KesslerPresidentSell15,000$10.95$164,250.00 12/23/2014Douglas A KesslerPresidentSell75,000$10.87$815,250.00 12/19/2014Douglas A KesslerPresidentSell35,486$10.57$375,087.02 11/28/2014Douglas A KesslerPresidentSell26,586$10.58$281,279.88 11/25/2014Douglas A KesslerPresidentSell6,400$10.57$67,648.00 11/24/2014Douglas A KesslerPresidentSell2,200$10.57$23,254.00 11/21/2014Douglas A KesslerPresidentSell89,328$10.31$920,971.68 11/12/2013Benjamin Md AnsellDirectorBuy6,260$8.00$50,080.00 11/6/2013Benjamin Md AnsellDirectorBuy5,000$8.50$42,500.00 (Data available from 1/1/2013 forward) About Ashford Hospitality Trust Ashford Hospitality Trust, Inc., (Ashford), together with its subsidiaries, is a self-administered real estate investment trust (REIT) focused on investing in the hospitality industry. The Company is engaged in direct hotel investments within the hotel lodging industry. Ashford owns its lodging investments and conducts its business through Ashford Hospitality Limited Partnership (Ashford Trust OP). Its hotels are primarily operated under the brands of Hilton, Hyatt, Marriott, Starwood and Intercontinental Hotels Group. Its hotels are located in the United States. The Company, through Remington Lodging, manages the Hampton Inn & Suites Gainesville hotel, which has 124 guestrooms, including 27 studio suites. The hotel's amenities include 1,700 square feet of meeting space, a boardroom, Saltwater Lap Pool and Spa, Jump Start fitness center and on-site parking. Ashford OP General Partner LLC is a wholly owned subsidiary of the Company. Headlines: (9/27) Ashford Hospitality Trust, Inc. To Go Ex-Dividend on September 28th (AHT) (9/28) Ashford Hospitality Trust Downgraded by Zacks to Hold (AHT) (10/6) Brokerages Set Ashford Hospitality Trust PT at $11.61 (NYSE:AHT) (9/30) Ashford Hospitality : Trust Sets Third Quarter Earnings Release And Conference Call Dates (11/3) Ashford Hospitality Trust (AHT) Declares Distribution of Ashford Inc. (AINC) (9/28) Is Ashford Hospitality Trust (AHT) Stock a Solid Choice Right Now? (9/25) Ashford Hospitality Trust Sets New 12-Month Low at $6.68 (AHT) (7/21) Ashford Hospitality Trust Is a Steal at These Prices (8/25) Why You Shouldn't Bet Against Ashford Hospitality Trust (AHT) Stock (6/18) Ashford Hospitality Trust, Inc. (AHT) to Spin Off Portfolio of 8 Luxury Hotels Industry, Sector and Symbol: Sector: Financial Industry: REIT - Hotel/Motel Sub-Industry: Specialized REITs Exchange: NYSE Symbol: AHT CUSIP: 04410310 Key Metrics: Previous Close: $7.0250 Day Moving Average: $7.26200 Day Moving Average: $8.46P/E Ratio: 2.70P/E Growth: 0.38Market Cap: $671.20MCurrent Quarter EPS Consensus Estimate: $1.42 EPS Additional Links: View AHT on Google FinanceView AHT on Yahoo FinanceView AHT's Company Profile on ReutersSearch for Ashford Hospitality Trust, Inc. on Google Ashford Hospitality Trust (NYSE:AHT) Chart for Saturday, October, 10, 2015


text:
I was watching a tv show (which sucks and ive only watched it once, called Bromwell High) where they made this joke, where a couple was talking about adopting a child. They were asked if they were infertile, but they answered that no, they were in fact super fertile, and the reason they wanted to adopt was that with all those homeless orphan kids lying around, it would be an insult to just have a child. It was just a joke, but later I started thinking about it and it actually made a lot of sense: with so many poor kids needing a home, doesn't it make sense that even fertile couples adopted children instead of birthing more?
I know that people want to have their own children, but it is just a suggestion. What do you think?


text:
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Lombardi and Lombardi, PA
New Jersey Personal Injury Lawyers906-1500 or (866) 523-3121
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Law Firm's Overview Free Consultation
Popescu Law Group
Family, Business and Employment Lawyer in Old Bridge, New Jersey(732) 952-5570
Popescu Law Group strives to provide the highest caliber of legal representation to our clients at reasonable cost. We have extensive experience and the resources to successfully handle the following matters: business law, family law, employment law and criminal defense in New York...
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Rispoli & Borneo, PC
Elizabeth, New Jersey Workers' Compensation, Criminal and Traffic Violation Attorneys(908) 353-0800
At Rispoli & Borneo, PC, our firm's experience is diverse and includes: personal injury; motor vehicle accidents; truck accidents; motorcycle accidents; workers compensation; criminal matters; drunk driving; traffic violations; and, medical malpractice.
Rispoli & Borneo,...
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Robert J. DeGroot, Attorney at Law
Newark, New Jersey Criminal Defense Lawyer(866) 970-0783 or (866) 970-0783
At the law offices of Robert J. DeGroot, we represent and advise individuals and business clients located in north and central New Jersey as well as New York City and Westchester since 1972. Our firm understands that at any level, facing any criminal charge is a serious matter that...
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Posted on 6 June 2014
- 17:30
The presenter famed for shows 'Man v. Food', 'Man v. Food Nation' and more recently, 'Fandemonium' will line-up as a striker alongside international greats Andrei Shevchenko and Alessandro Del Piero in the Rest of the World squad taking on England in the match to raise funds for UNICEF at Old Trafford on Sunday.
Edgar Davids is also in the Rest of the World squad, managed by Jose Mourinho, while another ex-Spur, Jamie Redknapp, is with England, who are managed by Sam Allardyce.
Soccer Aid is the brainchild of singer Robbie Williams and was first staged in 2006.
"First of all, thanks to Spurs for making this possible, it's an honour to represent the club and Spurs fans at Soccer Aid," said Adam, who enjoyed his first match at the Lane in March, a 1-0 win against Cardiff.
"I've Del Piero and Shevchenko as other members of our striking squad so I've a lot to live up to!
"I'll do my best impression of our great strikers like Sheringham, Defoe or Adebayor and whatever I can do to help spread the word of the beautiful game to the US, I'm all for.
"To Dare Is To Do is the way I think about it. Every time I step out at Old Trafford, I'll think 'the game is about glory'."
You can find out more on Soccer Aid by FOLLOWING THIS LINK…
An exclusive video of Adam at the Training Centre is available now FREE on Spurs TV...
8 August 2015
There was only one place to start when we asked fans for their opinions this week...
28 July 2015
Welcome to a new feature 'Spurs fans talk about...' where we'll canvas opinions of supporters on various topics throughout the season.
22 July 2015
As the build-up to our prestigious match against the MLS All-Stars in Colorado intensifies, Kyle Walker and Ben Davies go head-to-head in a unique MLS Challenge on Spurs TV.
View mobile site
© Tottenham Hotspur Ltd 2015. All rights reserved.
All photography copyright Getty Images (unless otherwise stated)


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"When you visit The Perfect Touch, you will not only feel relaxed,pampered, and gorgeous, you will know that our salon gives the best service ever!"
Every aspect of our salon is focused on developing the very best staff, techniques and product lines. For you to achieve the greatest salon experience.


text: Violet Mir:ror is USB RFID Enhanced-Reality Gizmo for Your GadgetsKit EatonFiled to: RFIDViolet mir:ror enhanced-reailtyToysvioletMirrorGadgetsWirelessConnectivity10/27/08 5:59amEditDeleteInvite manuallyPromoteDismissUndismissBlock for gizmodoHideShare to KinjaGo to permalinkYou won't be chanting "Mir:ror Mir:ror, on my desk" rhymes if you buy Mir:ror and want it to tell you some interesting info: instead you'll be waving your possessions over its USB-connected sensor, whereby small RFID stickers ID the objects, and prompt your computer to display enhanced-reality style info. For example, wave your brolly near it and get a weather forecast, or your TV remote to get tonight's schedule. So... it's kinda weird, but sounds strangely compelling. Which is perhaps no surprise when you learn it's made by Violet, who also bring us the weird-but-interesting animated internet "buddy" Nabaztag.The RFID bit is in the little Ztamps you stick to your gear, and the magic all happens through Violet's new website. The mir:ror can recognize many objects right off the bat, with dedicated stamps, but through the site you can configure more of your stuff to work with it. Tempted by a strange kind of gadget-driven augmented reality? Then it's out today for $70, though you only get the sensor, a skin for the sensor "puck", 2 nanotagz rabbits (looking like mini clones of Nabaztag himself) and 3 ztamps for that: you'll have to buy more RFID stickers for your other objects. [Dynamism via Technabob]7ReplyLeave a reply


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57 results for menus
Culture Briefing
The Menu - Beirut during Lent
Sacré bleu!
The Menu - The green alternatives
The Menu - Vancouver's beer paradise
Table manners
Monday 13 April
Does a new app that gives restaurants the ability to take advance payments for bookings make good business sense, or will it detract from the dining experience? Monocle's Josh Fehnert reports.
Launched earlier this year by Chicago-based restaurateur Nick Kokonas, Tock is an app making headlines in the hospitality industry. For starters, Tock proposes a new way of making reservations that recalibrates the balance…
Hooked for life
A man cannot live on turnips alone
Wednesday 18 December
Andrew Tuck's recipe for a tasty meal doesn't rely on locally sourced ingredients – in fact, the trend for reducing food miles is driving him bananas.
What's wrong with a banana? Well judging by the menus of nearly every new fancy-pants restaurant these days, quite a lot. Normally within the first few lines of overblown description they will have inserted those key words…
An acquired taste
Tuesday 6 May
New York is currently enjoying a new culinary combination – fish and chips in a pie. Tasty as it may be, Monocle's Tristan McAllister is wondering where the trend for mixing seemingly random dishes might end.
City dwellers are all too often treated to overhyped food hybrids borne of some weird chef's obsession with the cutting edge. Take the mix between a croissant and a doughnut for instance, or the surprising marriage of a pot…
The new brigade
Rare talent
Don't let the pre-made salad wraps get you down
Thursday 14 March
Although the Pret A Manger juggernaut continues to rumble on you can turn a corner this lunchtime and feast on some innovative street-food instead.
Walking to work yesterday I was surprised to discover a shiny new Pret a Manger food outlet preparing to launch about two blocks away from our office at Midori House. As a booming business, entrepreneurial success and…
Feeling picky
Monday 24 June
Whether it's dining out or ordering in, the array of choice now available to consumers is making decisions harder.
Hmmm. Decisions, decisions. Is there anything more attractive than a decisive person? Someone who can make decisions without the whiney disclaimer of, "Ooooh you choose, I can't make decisions, I'm so indecisive." Where…
Shredding the red tape
Monday 8 April
Our recently settled Hong Kong bureau chief is amazed to discover that tasks such as setting up utilities and buying a new phone can be simple, stress-free experiences.
I am happy to admit that I have no talent whatsoever when it comes to admin. Filling in forms, phoning call centres or setting up just about anything drives me up the wall. I never seem to have the right information on me…
Weekend Agenda
Saturday 5 November
Highlights of this weekend include a new music duo from Denmark, Korean film fest in London and a mouth-watering food app.
Highlights of this weekend include a new music duo from Denmark, Korean film fest in London and a mouth-watering food app.
Japanese brush up on their English
Friday 18 February
Verb conjugation; adverbial clauses; the future progressive: forget financial jargon, these are the words that may soon be found flying around the offices of Japan's banking world.
Verb conjugation; adverbial clauses; the future progressive: forget financial jargon, these are the words that may soon be found flying around the offices of Japan's banking world.
Yoga for dogs and cafés for cats
Friday 12 November
The model reclines on a camouflage pillow, a bandana tied casually around his neck above a red T-shirt with a white logo.
The model reclines on a camouflage pillow, a bandana tied casually around his neck above a red T-shirt with a white logo. So far, so Tokyo street-chic. Except for one thing: the model is not a human being, it's a dog.
Haus rules
Flower power
Tuesday 2 April
Japan's 'hanami' festival celebrates the annual arrival of cherry blossom as it sweeps the country. This year may have been a bit chilly but that hasn't cooled the warm glow created by this much-loved event.
Anyone who persists in thinking the Japanese are an inscrutable, reserved people should get themselves a blue tarpaulin and join in the two-week eating-and-drinking bonanza that is Japanese hanami: the annual celebration…


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Call our experts: 888.808.FINE
Select a quantity and printing method. Changes are easily made later.
Use this flat ivory card in cotton cardstock with rounded corners to write notes to family and friends. Add your name in the typestyle and ink color of your choice. A dune colored top-flap envelope is included.


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Cookeville, Tennessee Pet Friendly Hotels & Lodging
United States » Tennessee » Cookeville
Looking for a hotel in Cookeville, TN that you can bring your pet to? We made sure that each one of the hotels below are pet friendly, so you can enjoy your trip with your pet by your side! Once you have found a pet friendly hotel, you can book your stay instantly from our website or call 866-212-1803 to speak with a pet travel agent.
Browse Pet Friendly Hotels In Cookeville, Tennessee
Rates from
900 S Jefferson Avenue - Cookeville, TN (Map)
Best Western Thunderbird Motel is pet friendly. Guests are welcome to bring 2 pets no more than 80 pounds of pet. The pet fee is $20 per pet, per day.
Rates from
970 S Jefferson Avenue - Cookeville, TN (Map)
Pet guests are welcome at pet friendly Clarion Inn Cookeville. Each room can have no more than 2 pets. The pet fee is $10 per night.
Rates from
1296 S. Walnut - Cookeville, TN (Map)
Pet guests are welcome at pet friendly Cookeville-Days Inn. The pet fee is $15 per pet, per night plus $75 one-time cleaning fee.
Rates from
1151 South Jefferson Avenue - Cookeville, TN (Map)
Country Inn & Suites By Carlson, Cookeville, TN allows pets to accompany their people at their pet friendly accommodation. The pet fee is $25 per pet, per night.
Rates from
1814 Salem Rd - Cookeville, TN (Map)
Fall Creek Inn welcomes four-legged guests at their pet friendly accommodation. Up to 2 pets are allowed in each room. The pet fee is $10 per pet, per night.
Rates from
1292 S Walnut Avenue - Cookeville, TN (Map)
Pets stay FREE of charge. One well-behaved family pet per room. Must notify front desk upon arrival. Guest is liable for any damages. In consideration of all guests, pets must never be left unattended in guest room.


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Shipping Charges Priced in Cart
Product Information:
The CHIP Barstool, winner of the Good Design® Award from the Chicago Athenaeum, showcases Kotilainen's talent and creative vision. With the same clean, graceful lines that distinguish the innovative CHIP chair, the CHIP Barstool features a sleek, minimal appearance that makes it a highly adaptable piece.The CHIP Barstool features form-pressed thin plywood sheets on a steel frame, resulting in a physically and visually light aesthetic. Its distinct and harmonious lines enhance any interior space either individually or grouped in rows or clusters. The stackable stool is ideal for cafeterias, breakout areas and hospitality applications. Its durability and style make it ideal for public spaces, offices, cafes and bars
Additional Documents
Weights & Dimensions
|Seat Style: Square
|Frame Finish: Chrome-plated
|Distressed: No
Frame Material: Metal
|Seat Material: Wood
|Number of Items Included: 1
|Stackable: Yes
Seat Back Included: Yes
|Cushions Included: No
|Arms Included: No
Legs Included: Yes
|Footrest Included: Yes
|Casters Included: No
|Nailhead Trim: No
|Commercial Use: No
About the ManufacturerWith a long history of design innovation for the home, workplace, and in textiles, Knoll continues to play a large part in the foundations of Modern Design. Founded in 1938 by Hans Knoll and continued after his death by his wife Florence Knoll, the company has produced a long line of award-winning and museum worthy designs from virtually every top designer in modern design.
More About This Product
Shipping Charges Priced in Cart
Ships to:
Ships via: Front Door: Drop-Off Delivery with Upgrade Options
Enter your shipping zip or postal code to calculate shipping estimatesGet Delivery Estimate
We want you to love it. If you don't, you may return your purchase within 30 days of delivery. All you need to do is visit our Self-Service Return Center for instructions. Return credits are issued within 24 hours once the item is received and inspected. Please note that shipping charges are non-refundable. The cost of return shipping will be deducted from your refund. 30-Day Return Policy
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STARmeterSEE RANK
Down 469 this week
Michael E. Knight
Michael E. Knight was born on May 7, 1959 in Princeton, New Jersey, USA as Michael Edward Knight. He is an actor, known for All My Children (1970), Date with an Angel (1987) and Hexed (1993). He was previously married to Catherine Hickland. See full bio »
More at IMDbPro » Contact Info: View agent
2 photos | 4 videos | 37 news articles »


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Brazil's Straw Hat project helps women leave abusive situations
Has Russia saved the Assad regime from collapse?
04 Dec 2006 02:51 GMT
There were long queues to many polling stations during the day and although voting had officially ended in some areas at 1600 local time, by law polling stations could not shut their doors until the last person in line had voted.Chavez favouriteThere is a very strict law in Venezuela preventing exit polls being broadcast or published in any way until the electoral commission has sorted through over half the ballots and made its initial findings on how the vote is going.
However, Aljazeera's Rob Reynolds in Caracas has been speaking to people who have been observing the way voting has been going and talking to voters and they have said that so far there is nothing in the trend that would contradict earlier polls predicting a very strong victory for Chavez.
Security sources reported no serious incidents during voting. Extra forces had been deployed in case what had been a bitter campaign spilled over into violence.
Chavez supporters were upbeat as they turned out to voteThere had been rumours of fraud by some in the Rosales' camp but election officials reported no irregularities.
Highlighting the high voter turnout Chavez earlier said he expected "democratic results".Divided country
Despite his lead in the polls, the campaign has highlighted stark divisions in Venezuela and both extremes of view were found in many of the queues of waiting voters.
In the neighbourhood of San Bernadino, where middle class streets surround a squalid slum Margarita Budik, a retiree and Rosales supporter called the election the most important in the 50 years since she first voted.
"This election will decide whether one can live here, or whether we have communism," the 68-year old said.
In the same queue, storekeeper Julio Cesar Perez, 59, wore a bright red shirt, the colour of Chavez supporters.
"This shirt says it all," he said with a smile as he awaited his turn near an anti-imperialist mural displaying a caricature of Uncle Sam and the words, "the fatherland cannot be sold".Chavez chargeChavez had earlier accused Washington of seeking to sow discord in Venezuela, and denounced his electoral rival as a lackey of the "US empire".
Chavez, 52, has pledged to consolidate his self-styled revolution and launch a new socialist era if re-elected.
Rosales claims Chavez is seeking to turn Venezuela into a communist state and called him "a puppet seated on Castro's lap".
Rosales says Chavez is wasting thecountry's oil wealth He has managed to unify a previously discordant Venezuelan opposition and accuses his rival of squandering the country's oil wealth.
Sixteen million people were eligible to vote in the presidential election, including 17,000 who were registered to turn out and vote in Miami, Florida.
The vote ended a busy electoral year in the Latin American region which has seen five left-wing or left-leaning presidents elected into office.
Source: Al Jazeera and agencies
Analysis of some of the leading left-wing politicians in Latin America.
Politics, US & Canada, United States
Venezuela's president says an attempt to kill a presidential opponent has been foiled.
Twice the size of Paris, the open-air Iwahig Prison and Penal Farm offers a unique approach to reforming criminals.
Prisoners, Philippines, Crime
As the battle over Kunduz rages, US may be forced to extend troop deployment after 14 years of warfare with the Taliban.
War & Conflict, United States, Afghanistan
Military intelligence ordered major companies to steer clear of two independent newspapers with ad revenue, sources say.
Media, Bangladesh, Politics
Enbridge Energy is eyeing a major pipeline in Minnesota state, but the project faces fierce environmental opposition.
Environment, Oil spill, Energy
We speak to former Israeli Prime Minister Ehud Olmert, and ask a former KGB general about Russia's air strikes in Syria.
War & Conflict, Middle East, Israel
The names of Newton, Galileo and Copernicus are well known, but how have the great Islamic thinkers of the middle ages contributed to the science of today?
In a Delhi slum, puppeteers, musicians, jugglers and acrobats try to unite as they wrangle with an approaching eviction.
Business & Economy, Arts & Culture, Poverty & Development
101 East follows the lives of seven people in Nanjing and asks what they think of the direction their country is taking.
Politics, Asia Pacific, China


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Hi, welcome to Vale of Belvoir CAMRA online. We aim to keep you up to date with all the beer & pub related happenings in and around the Vale of Belvoir. Read and enjoy - feedback always (ish) welcome!
sec. VoB CAMRA
Site Content
The views expressed on this web site are not necessarily those of the Campaign for Real Ale Ltd. Whilst every effort is made to ensure that
the information on this site is accurate and up to date, no responsibility for errors and omissions or misfortune due to the content of this site can be accepted. Links to external servers do not imply any official CAMRA endorsement of the opinions or ideas
expressed therein, or guarantee the validity of the information provided. Links to commercial sites are in no way an endorsement of any vendor's products or services. The nature of blogging means that many posts on any of the news pages will be based
on rumour or heresay and contain author's personal views. No responsibility for errors and omissions or misfortune due to the content of the blog can be accepted.
Was in Crown Sproxton Sat evening. They had 4 pumps on. I had Grainstore Rutland Osprey and Cathedral Heights Lincoln IPA. Alan's very passionate about his beer
Opening weekend at The Geese and Fountain, Croxton Kerrial, 1st - 2nd August. Morris dancing on the Saturday, Ceilidh band on the Sunday.
Hope people won't mind me making a quick plug for our opening weekend at The Geese and Fountain, Croxton Kerrial, August 1st and 2nd. We're in the Vale of Belvoir CAMRA area, which I think makes us part of Nottingham branch.We'll have a beer list for th


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It took 14 innings to get a conclusion to Wednesday night's game for the Los Angeles Dodgers but Hanley Ramirez and A.J. Ellis would make sure it would go no further. The two would hit a pair of solo home runs in the top of the 14th to give the Dodgers a 7-5 victory and the sweep over the Arizona Diamondbacks.
Finishing out the road trip in style with a great team win and a 7-2 record the Dodgers have now reached .500 on the season for the first time since April 30th. Not only have they come back from 12 games under .500 but they are now only 1.5 games back of the first place Diamondbacks.
Neither starting pitcher got the job done particularly well on the night. For only the second time this year Dodgers starter Hyun-Jin Ryu didn't at least complete six innings of work. Also for only the second time, Ryu gave up five earned runs in a game as he allowed seven hits and two walks.
The Dodgers found themselves in 2-0 hole after three innings due to an Aaron Hill solo homer and sac fly. Earlier in the season getting down early would have been about all for a Dodgers team that showed almost no ability to come back. However, that hasn't been the case of late for a team that is now 15-3 in its last 18 games.
With a score of 2-1 Diamondbacks in the fifth, Ramirez, who had his 19-game hit streak snapped last night, launched a two-run double into deep center that Vin Scully described as "shot out of a howitzer," to give the Dodgers a 3-2 lead.
The Diamondbacks would answer quickly with Paul Goldschmidt smacking a two-run double of his own to take the lead back at 4-3. The lead would be pushed to 5-3 when Goldschmidt would come around on a Martin Prado single.
It became a battle of the bullpens after the fifth and the Diamondbacks pen would let the Dodgers back in the game. Adrian Gonzalez would hit his 14th homer of the season in the eighth off David Hernandez to pull the Dodgers within one.
Gonzalez would play a crucial role in the ninth with two outs and a 3-2 count against closer Heath Bell. With the Dodgers down to their last strike Gonzalez would work the walk to bring up the hottest man on the planet in Ramirez. The Dodgers cleanup hitter would single to center field to bring up A.J. Ellis with two on. Ellis would single to tie the game and eventually send the game to extra innings.
Ellis is currently on a nine game hitting streak that has seen him hit .385 with 11 RBI.
By the time the 14th inning rolled around the Dodgers bullpen had already tossed eight innings only allowing two hits. Chris Withrow would throw three of those innings to really give his team every opportunity to win it. Kenley Jansen took care of the final two innings to nail down the victory.
The Colorado Rockies will be waiting at Dodgers Stadium to finish the first half with a four game series starting Thursday night.
WP: Kenley Jansen (3-3)
LP: Josh Collmenter (4-2)


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Mr. Gretchev
I've been using GLFW 2.x for some time now and recently decided to see what GLFW 3.0 had going for it. I'm really digging the multi-monitor support and some of the other minor enhancements.
I want to start using 3.0 for a project where I target on having a stable, mostly feature complete build completed about a year out from now. Is there a timeline on when 3.0 will have its first stable release?
Camilla Löwy
There is no fixed schedule, but the release is approaching.